Journal Article

FOXO regulates the expression of antimicrobial peptides and promotes phagocytosis of hemocytes in shrimp antibacterial immunity

Zhao, Xiao-Fan, Yang, Ming-Chong, Wang, Jin-Xing, Li, Cang, Hong, Pan-Pan

2021

Overview

Invertebrates rely on innate immunity, including humoral and cellular immunity, to resist pathogenic infection. Previous studies showed that forkhead box transcription factor O (FOXO) participates in mucosal immune responses of mammals and the gut humoral immune regulation of invertebrates. However, whether FOXO is involved in systemic and cellular immunity regulation in invertebrates remains unknown. In the present study, we identified a FOXO from shrimp ( Marsupenaeus japonicus) and found that it was expressed at relatively basal levels in normal shrimp, but was upregulated significantly in shrimp challenged by Vibrio anguillarum . FOXO played a critical role in maintaining hemolymph and intestinal microbiota homeostasis by promoting the expression of Relish , the transcription factor of the immune deficiency (IMD) pathway for expression of antimicrobial peptides (AMPs) in shrimp. We also found that pathogen infection activated FOXO and induced its nuclear translocation by reducing serine/threonine kinase AKT activity. In the nucleus, activated FOXO directly regulated the expression of its target Amp and Relish genes against bacterial infection. Furthermore, FOXO was identified as being involved in cellular immunity by promoting the phagocytosis of hemocytes through upregulating the expression of the phagocytotic receptor scavenger receptor C ( Src ), and two small GTPases, Rab5 and Rab7 , which are related to phagosome trafficking to the lysosome in the cytoplasm. Taken together, our results indicated that FOXO exerts its effects on homeostasis of hemolymph and the enteric microbiota by activating the IMD pathway in normal shrimp, and directly or indirectly promoting AMP expression and enhancing phagocytosis of hemocytes against pathogens in bacteria-infected shrimp. This study revealed the different functions of FOXO in the mucosal (local) and systemic antibacterial immunity of invertebrates.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 1-Phosphatidylinositol 3-kinase / AKT protein / Animals / Antiinfectives and antibacterials / Antimicrobial agents / Antimicrobial peptides / Autophagy / Bacteria / Bacterial infections / Biological activity / Biology and Life Sciences / Cell cycle / Crustaceans / Deoxyribonucleic acid / Development and progression / DNA / DNA repair / E coli / Forkhead protein / Forkhead Transcription Factors - genetics / Forkhead Transcription Factors - metabolism / FOXO1 protein / Genetic aspects / Growth factors / Hemocytes / Hemocytes - immunology / Homeostasis / Immune response / Immunity / Immunity, Innate / Infections / Insect immunity / Insects / Insulin / Insulin-like growth factor I / Invertebrates / Janus kinase / Kinases / Leukocytes (neutrophilic) / Mammals / Medicine and Health Sciences / Microbiota / Natural killer cells / Neutrophils / Pathogens / Penaeidae - genetics / Penaeidae - immunology / Penaeidae - microbiology / Peptides / Phagocytosis / Phagocytosis - immunology / Phosphorylation / Phylogenetics / Physiological aspects / Polyclonal antibodies / Pore Forming Cytotoxic Proteins - metabolism / Protein-serine/threonine kinase / Proteins / Shrimps / Threonine / Vibrio - physiology